Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton

An in vitro assay system was developed to assess the potency of the human i nnate immune system by measurement of IL-12, IL-18, IL-10 and IFN gamma in the supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-s timulated blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and 4, and activates monocytes to macrophages (M phi), and immature dendri tic cells to mature antigen-presenting cells (APC). This system was found t o allow the discrimination of immune suppressive states in patients with lu ng cancer from normal immune states in light of the cytokine profile. The f ollowing results were deduced from analyses of BCG-CWS -stimulated blood sa mples of lung cancer patients with reference to normal subjects. (1) The le vels of production of IFN gamma and IL-10 by lymphocytes were decreased. (2 ) IL-12 p40 production by monocytes/M phi was upregulated, while that of IL -10 was downregulated. (3) IL-18 was detected in all patients in a range si milar to normal subjects. (4) Responses of lymphocytes to IL-2 and IL-18 in terms of IFN gamma production were diminished. (5) The upregulated IL-12 l evels were recovered to within the normal range in most patients after tumo r resection. (6) Male patients showed more severe suppression of IL-12/IL-1 8-mediated IFN gamma production than female patients. Thus, the lesser IFN gamma production observed in patients' blood with high IL-12 p40 levels in response to BCG-CWS may reflect the production of p40 dimers or IL-23 inste ad of p70, or the presence of some unknown pathways to prohibit the interfa ce between the innate and acquired immune systems. BCG-CWS-mediated Toll si gnaling may participate in IFN gamma induction for lymphocytes through M ph i /APC IL-12/IL-18 modulation. (C) 2001 Elsevier Science B.V. All rights re served.